Dr. Durie, chairman of the board of the International Myeloma Foundation – http://www.myeloma.org - has just published the following paper on the connection between toxins, including those in the marine environment, with multiple myeloma. It is likely that correlations to other forms of cancer will emerge. Dr. Durie’s paper won recognition as a “Best of ASH” abstract at a recent meeting of the American Society of Hematologists.

THE INTERNATIONAL MYELOMA FOUNDATION IDENTIFIES POTENTIAL LINK BETWEEN GENETIC PATHWAYS AND ENVIRONMENTAL RISKS FOR MYELOMA

North Hollywood, CA, and Atlanta, GA, December 11, 2007 - The International Myeloma Foundation (IMF) http://www.myeloma.org — today said findings from its myeloma DNA bank identified genetic links to bone disease in multiple myeloma, a cancer of cells in the bone marrow, that in some cases can also include bone deterioration. These findings also may both support and explain associations that have been observed between environmental toxins such as dioxins and benzene, and an increased risk for myeloma. The findings were made with resources from Bank On A Cure® (BOAC), the world's first repository of DNA samples created to advance the understanding of myeloma. They were presented at the 49th Annual Meeting of The American Society of Hematology in Atlanta on December 11th.

The study found that genetic pathways associated with the ability to neutralize environmental toxins are defective in patients with classic myeloma (myeloma with bone involvement). These pathways are identified as specific segments of genes called single nucleotide polymorphisms or SNPs that are known to be associated with toxin metabolism and DNA repair. These findings are in line with observations of patient populations and groups of workers including firefighters that had previously demonstrated a correlation between increased risk for myeloma and exposure to hydrocarbons and related chemicals.

"Identifying these genetic pathways was unexpected," said Brian G.M. Durie. M.D., chairman of the International Myeloma Foundation and lead author of the BOAC presentation. "We were looking at bone biology and the SNPs associated with toxin metabolism fell into place. Now, working back through the gene pathways, we have a robust model of myeloma bone disease that may explain the epidemiological observations."

Dolphins and humans are exposed to the same toxins in seafood. Over 2 billion people worldwide rely on seafood as their major source of protein and 60% of people live in coastal areas. Resident coastal dolphins are exposed to marine pollution in the same fashion as humans who frequently consume seafood, thus any indication of disease in dolphins has implications both for humans who eat regularly from the same areas and/or are otherwise exposed to the same toxins.

Although ecotoxicologic studies of marine environments are very complex, (Irwin: Aquatic Mammals 31:195-225, 2005), the bottlenose dolphin is a sentinel species for biomonitoring purposes. Tissue levels of many known carcinogens such as DDT, DDE, dioxins (e.g. PCDDs and 2,3,7,8 TCDD), BaP, PAHs, and more recently PFC and PBDEs (water repellants and fire retardants), reflect bioaccumulation in both dolphins and humans. Target sites where human and dolphin disease have been contrasted and compared are: North America (Alaska; Puget Sound; San Francisco Bay; Gulf Coast and Florida; St. Lawrence Seaway); Japan (Osaka Bay); Sweden; Coastal UK and Hong Kong (Pearl River estuary). For Alaska, Florida, Japan, Sweden and coastal UK, there are highly significant correlations between fish contamination/ consumption and excess risk of human myeloma. In Alaska, Inuit men eat contaminated fish, have high organochloride (dioxins) levels in blood and tissues and an increased risk of myeloma. Likewise for Swedish fisherman comparing Baltic (more contamination) versus west coast levels of dioxins and myeloma. In Japan, a case control study provides a highly significant odds ratio of 5.89 for agriculture/ fisheries as occupational factors. A separate study gives an annual age adjusted incidence of 7.03/100,000 for the Osaka Bay fishing region. Around Lake Okeechobee Florida an incidence rate of 6.52/100,000 correlates with both contamination and commercial fishing licenses.

Although dolphins share most human mammalian genes, including CYP1A and CYP2B, they lack the ability to adequately catabolize type I and II dioxins, which therefore preferentially accumulate. Unfortunately, observed results of these bioaccumulations are suppressed immunity, infections and cancers particularly Bcell lymphomas and myeloma-like immunoblastic lymphomas (Bossart: J. Vet Diagn Invest 9: 454-458, 1997). This pattern of diseases in turn corresponds with the local and systemic effects exemplified in Balb/c mice during pristane-induced plasmacytogenesis and in humans exposed to toxins.

Newly recognized persistent organic pollutants such as water repellants (PFCs) and flame-retardants
(PBDEs) are a particular concern, both because of rapid recent bioaccumulation in dolphins with associated disease manifestations plus the potential for wide global dispersal and diverse routes of human exposure. Numerous consumer goods contain PBDEs, including electronics, carpets, furniture and textiles. Genetic studies help refine probability calculations to assess risk using the union rule for independent events.

Studies are now underway to correlate recent bioaccumulations in dolphins and humans, genetic
predisposition and myeloma onset. Probability calculations for risk of developing myeloma will support
interventions to reduce both contamination of the marine environment and elimination of human toxin
exposures.